Cases reported • Carcinoma In Situ; Carcinoma, Intraepithelial; Carcinoma, Preinvasive

1/335. Fine-needle aspiration cytology of cystic hypersecretory ductal carcinoma in situ of the breast: a case report.

Cystic hypersecretory intraductal carcinoma is an unusual, cystic form of intraductal breast carcinoma affecting middle-aged women. Cytopathologists have rarely encountered this lesion, with only 2 other cases having been previously reported (Colandrea et al., Arch Pathol Lab Med 1988:112:560-563; Kim et al., Acta Cytol 1997;41:892-896). In our cases, the cytologic findings of both air-dried, Diff-Quick-stained and ethanol-fixed, Papanicolaou-stained smears are presented. The cytologic hallmarks of this entity include the presence of a few scattered epithelial cells with bland nuclear morphology in a background of extensive, amorphous, pink-staining material. Cytomorphologically, the differential diagnosis includes other entities containing pink-staining material such as colloid carcinoma, mucocele-like lesion of the breast, and benign fibrocystic change.

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2/335. Human papillomavirus types 16 and 39 in a vulval carcinoma occurring in a woman with Hailey-Hailey disease.

A woman with Hailey-Hailey disease, suffering from carcinoma of the vulva, was examined by histology and for the presence of human papillomavirus (HPV) DNA by polymerase chain reaction (PCR) and in situ hybridization. Our diagnosis by histological examination revealed the vulval carcinoma to be a squamous cell carcinoma (SCC), adjacent to lesions of Hailey-Hailey disease and severe dysplasia/carcinoma in situ [vulval intraepithelial neoplasia (VIN) III]. The PCR with consensus primers for the L1 region (L1-PCR) successfully amplified HPV DNA using total DNA extracted from formalin-fixed and paraffin-embedded tissue specimens. Restriction fragment length polymorphism analysis and sequencing of L1-PCR products revealed HPV types 16 and 39. HPV 16-specific primers for the E6 region identified HPV 16 DNA. in situ hybridization analysis with biotinylated HPV 16 and 39 dna probes revealed the presence of the HPV 39 genome in the nuclei of the tumour cells in the SCC. These results indicate that HPV 16 and 39 are associated with lesions in vulval carcinoma. Regarding the patient's susceptibility to infection in the case of Hailey-Hailey disease, there is a possibility that HPV was inoculated into the lesions of Hailey-Hailey disease and induced those of VIN III and SCC.

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3/335. Gonadal histology with testicular carcinoma in situ in a 15-year-old 46,XY female patient with a premature termination in the steroidogenic acute regulatory protein causing congenital lipoid adrenal hyperplasia.

Mutations in the steroidogenic acute regulatory protein (StAR) gene cause congenital lipoid adrenal hyperplasia, characterized by diminished or absence of adrenal and gonadal steroids, resulting in severe adrenal insufficiency and ambiguous or complete female external genitalia in genetic males. We report on a 15-yr-old 46,XY phenotypic female, referred because of lack of pubertal development. ACTH and gonadotropin concentrations were elevated; and aldosterone, cortisol and its precursors, and sex steroids before and after stimulation were below the lower limit of detection. In the StAR gene, a homozygous nonsense mutation (TGG --> TAG) in exon 7 (W250X) was identified. Histologic examination after gonadectomy showed seminiferous tubules containing immature sertoli cells and a few single germ cells with positive placental-like alkaline phosphatase immunoreactivity, indicating carcinoma in situ. This is the first report on testicular morphology, at a pubertal age, in a female patient with 46,XY karyotype and a mutation in the StAR gene, in whom gonadal neoplasia had developed.

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4/335. Squamous carcinoma in situ of the skin containing premelanosomes, with melanocytic colonization of the tumor.

Premelanosomes in nonmelanocytic epithelial neoplasms and "colonization" of nonmelanocytic tumors by melanocytes are two phenomena rarely documented in the literature. We report a squamous carcinoma-in-situ of skin displaying both phenomena. light microscopy showed clusters of tumor cells in the epidermis, some of which contained melanin. Dendritic melanocytes were admixed with the tumor cells. No ulceration was present. Immunoperoxidase stains for keratin showed no staining of tumor cells. Some nondendritic cells stained for HMB-45, consistent with a melanocytic lesion. Electron microscopy showed two cell types, one with desmosomes, tonofilaments, and premelanosomes and a second dendritic type with only premelanosomes. Premelanosomes were also present free in the intercellular space. These findings suggest that premelanosomes may first be discharged by melanocytes into the intercellular space and are then phagocytosed by the neoplastic cells. Thus the presence of premelanosomes in a tumor cell is not pathognomonic for melanoma or other neural crest tumors.

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5/335. Ocular surface neoplasia masquerading as chronic blepharoconjunctivitis.

PURPOSE: To present the clinical characteristics and difficulties in the diagnosis of various ocular surface malignancies mimicking features of chronic blepharoconjunctivitis and to summarize the current therapeutic approach and prognosis of patients. methods: Six patients with slowly evolving signs of persistent inflammation underwent a conjunctival biopsy after a prolonged course of medical treatment. The medical records of the patients were reviewed. RESULTS: Histopathologic examination of the biopsy specimens revealed intraepithelial squamous neoplasia (one patient), invasive squamous cell carcinoma (one patient), sebaceous carcinoma (two patients), and conjunctival lymphoma (two patients). CONCLUSION: Although uncommon, ocular surface malignancies may involve the conjunctiva diffusely and present as chronic conjunctivitis. A high index of suspicion and an early histopathologic examination are essential to not delay diagnosis.

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6/335. Squamous cell carcinoma of the penis arising on lichen sclerosus et atrophicus.

Squamous cell carcinoma of the penis arising on lichen sclerosus et atrophicus is rarely reported. A case is described in a 63-year-old man who had been diagnosed of lichen sclerosus et atrophicus 3 years before. The previously reported cases, the association of these diseases in women and men, and the possible pathogenesis are discussed.

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7/335. Squamous cell carcinoma with necrotizing scleritis.

PURPOSE: To report on a case of limbal squamous cell carcinoma (SCC) with necrotizing scleritis in a young, previously healthy, white Australian male. methods: A 31-year-old man presented with a left limbal lesion intermittently causing a red eye and foreign body sensation. He had enjoyed surfing for many years. Repeat hiv tests were negative and the lesion was biopsied. RESULTS: biopsy showed a well-differentiated SCC apparently arising in an intra-epithelial (in situ) carcinoma of the conjunctiva. The lesion was excised and a corneoscleral graft repair was performed. CONCLUSION: The present case highlights the potential for a significant increase in the prevalence of ocular surface neoplasia in healthy young people who have had excessive UV-B exposure.

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8/335. Observations on the histopathologic diagnosis of microinvasive carcinoma of the breast.

Our histopathologic criteria for diagnosing microinvasive carcinoma of the breast may be enunciated as follows: (1) cytologically malignant cells in the stroma associated with in situ carcinoma, (2) absence of basement membrane and myoepithelial cells around the invasive cells, (3) frequent accompanying stromal alterations in the form of myxomatous change and loosening of connective tissue, and (4) the frequent presence of an inflammatory cell infiltrate composed of lymphocytes and plasma cells. Most or all of these four features are present in cases of ductal microinvasive carcinoma of the breast, but the lobular type is not likely to be accompanied by stromal changes or a lymphoplasmacytic cell infiltrate. The minimum information regarding microinvasive carcinoma of the breast that should be conveyed in the final pathology report includes size as measured by the ocular micrometer or a statement that microinvasion refers to a lesion smaller than 1 mm, the number of foci of invasion, and the spatial distribution of the invasive foci. The nuclear grade of the invasive cells and the size, type, and nuclear grade of the accompanying DCIS should be specified. The status of margins, presence of vascular channel involvement (a rarity in microinvasive carcinoma of the breast), and degree of proliferative changes in adjacent nonneoplastic breast tissue should be reported. Immunostains for basement membrane and myoepithelial cells may be helpful in the diagnosis of microinvasive carcinoma of the breast. Sclerosing lesions such as radial scar and sclerosing adenosis can simulate microinvasive carcinoma of the breast, especially when the latter is associated with in situ carcinoma. Caution should be exercised in cases wherein in situ malignant cells may be dislodged by needling procedures or during dissection of the excised specimen. cautery-induced artifacts also hinder optimal histologic assessment. In some cases, it is virtually impossible to determine if true invasion is present, and the statement "microinvasive carcinoma of the breast cannot be entirely excluded" may be employed as a last resort. We consider the latter diagnosis to be the last refuge of the diligent pathologist and do not recommend it unless all diagnostic measures, including examination of deeper levels and supplemental stains, have been exhausted. It may be necessary to seek an expert opinion in "difficult" cases, particularly in the event that therapeutic decisions are to be based on the determination of invasion. From a clinical perspective, the management of microinvasive carcinoma of the breast ought to be dictated by the individual circumstances in each case. Based on currently available data, which admittedly suffer from lack of diagnostic uniformity, the vast majority of patients with microinvasive carcinoma of the breast will be node-negative and can look forward to an excellent prognosis. It is hoped that since the UICC has adopted a previously recommended definition of microinvasive carcinoma of the breast, prospective or retrospective studies with uniform diagnostic criteria will be conducted that will enable more definitive conclusions regarding the treatment and prognosis of microinvasive carcinoma of the breast.

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9/335. Conjunctival epithelial neoplasias in organ transplant patients receiving cyclosporine therapy.

PURPOSE: To report two cases of conjunctival epithelial neoplasias occurring after long-term systemic cyclosporine therapy in organ transplant recipients. methods: Case report. Each patient underwent an excision of an extensive limbal conjunctival lesion, followed by a histopathologic analysis. RESULTS: Histopathologic examination results revealed a carcinoma in situ and a squamous cell carcinoma in patients 1 and 2, respectively. recurrence occurred in patient 1, who needed topical mitomycin C 0.02% treatment. No recurrence was observed in patient 2 after a follow-up of 24 months. CONCLUSION: To our knowledge, these are the first reported cases of its kind after longterm systemic cyclosporine therapy. Further studies will be needed to determine the exact role of cyclosporine in the induction of conjunctival epithelial neoplasias and the need for regular ophthalmologic examination of transplant recipients.

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10/335. Diagnostic value of anti-alpha FP antibody levels in a metastatic germ cell tumor of unknown primary site.

BACKGROUND: A 21 year old man with a metastatic germ cell tumor of unknown primary not responding to chemotherapy was scheduled to have a blind bilateral orchiectomy to eradicate the possible primary site although palpation and ultrasonography of the testicles had always been normal. METHOD: The patient underwent a radioimmunoscintigraphy with Anti-alpha FP antibody scan (AFP-Scan). RESULTS: On the basis of the scintigraphic results the patient underwent a left orchiectomy and additionally removal of the lymph node metastases. histology revealed the presence of an in situ carcinoma in the left testis and a mixed tumor present in the abdominal lymph node metastases. Fluorescent in situ hybridization on tumor cells did not show any abnormalities related to chromosome 12, a finding connected with the somatic type of germ cell tumors. CONCLUSION: Anti-alpha FP antibody scan was helpful in detecting the primary site and saving the life of the patient without resulting in hypogonadism.

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